BAFF System in Rheumatoid Arthritis: from Pathobiology to Therapeutic Targets

Ancuţa, Codrina; Pomirleanu, Cristina; Mihailov, Claudia; EugenAncuta,; Opriş, D.

doi:10.5772/66580

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…6 | THE BAFF/APRIL IN RA Neutrophils are dominant cells and sources of BAFF in the joint. In the early phase of RA disease, the BAFF is produced significantly by dendritic cells, which leads to an increase in the proliferation of B cells; macrophages, on the other hand, are considered to be the source of BAFF in the confirmed phase of the disease (Ancuta et al, 2017). Through affecting dendritic cells, BAFF increases the production of inflammatory cytokines such as IL-1 and IL-6, augmenting the differentiation of T cells toward TH17.…”

Section: Nogo-66 Receptormentioning

confidence: 99%

The role of BAFF and APRIL in rheumatoid arthritis

Shabgah

Sarabi

Tavakkol‐Afshari

et al. 2019

Journal Cellular Physiology

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Development and activation of B cells quickly became clear after identifying new ligands and receptors in the tumor necrosis factor superfamily. B cell–activating factor (BAFF) and a proliferation‐inducing ligand (APRIL) are the members of membrane proteins Type 2 family released by proteolytic cleavage of furin to form active, soluble homotrimers. Except for B cells, ligands are expressed by all such immune cells like T cells, dendritic cells, monocytes, and macrophages. BAFF and APRIL have two common receptors, namely TNFR homolog transmembrane activator and Ca2+ modulator and CAML interactor (TACI) and B cell–maturation antigen. BAFF alone can also be coupled with a third receptor called BAFFR (also called BR3 or BLyS Receptor). These receptors are often expressed by immune cells in the B‐cell lineage. The binding of BAFF or APRIL to their receptors supports B cells differentiation and proliferation, immunoglobulin production and the upregulation of B cell–effector molecules expression. It is possible that the overexpression of BAFF and APRIL contributes to the pathogenesis of autoimmune diseases. In BAFF transgenic mice, there is a pseudo‐autoimmune manifestation, which is associated with an increase in B‐lymphocytes, hyperglobulinemia, anti‐single stranded DNA, and anti‐double‐stranded DNA antibodies, and immune complexes in their peripheral blood. Furthermore, overexpressing BAFF augments the number of peripheral B220+ B cells with a normal proliferation rate, high levels of Bcl2, and prolonged survival and hyperactivity. Therefore, in this review article, we studied BAFF and APRIL as important mediators in B‐cell and discussed their role in rheumatoid arthritis.

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Section: Nogo-66 Receptormentioning

confidence: 99%

The role of BAFF and APRIL in rheumatoid arthritis

Shabgah

Sarabi

Tavakkol‐Afshari

et al. 2019

Journal Cellular Physiology

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“…Our results could be explained on the basis that in the early phase of RA disease, the APRIL is produced significantly by dendritic cells, which leads to an increase in the proliferation of B cells; and ultimately, B cells are differentiated by APRIL producing autoantibodies (Shabgah et al 2019). Macrophages, on the other hand, are considered to be the source of APRIL in the confirmed phase of the disease (Ancuta et al 2017), causes the accumulation of plasma cells in the joint, further increasing the production of inflammatory cytokines such as TNF, IL-1, and IL-6 (Zhao et al 2014).…”

Section: Discussionmentioning

confidence: 77%

Serum a proliferation-inducing ligand and MicroRNA-223 are associated with rheumatoid arthritis: diagnostic and prognostic implications

Taha

Shaker

Abdelsalam³

et al. 2020

Mol Med

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Background Current blood-based tests for rheumatoid arthritis (RA) have inherent limitations, necessitating the need for additional new biomarkers for its diagnosis and monitoring disease activity and responsiveness to therapy. MicroRNAs (miRNAs) and a proliferation-inducing ligand (APRIL) are deregulated in RA and were linked to its pathogenesis. This study investigated serum levels of APRIL, miR-223 and miR-155 in RA patients, their potential as diagnostic and prognostic biomarkers, and their correlation with disease activity and clinicopathological data. Methods One hundred and twenty Egyptian patients with RA and 130 healthy controls were included. Serum miRNAs and APRIL were assayed by RT-qPCR and ELISA, respectively. Results Serum APRIL and miR-223 were significantly upregulated, while miR-155 was unchanged in RA patients compared to controls. Serum miR-223 discriminated RA patients from controls with AUC = 0.85, whereas serum APRIL superiorly distinguished the two groups with AUC = 1 (sensitivity and specificity = 100% at cutoff> 4.19 ng/ml) by receiver-operating-characteristic analysis. Serum miR-223 was a significant predictor for RA diagnosis in multivariate logistic regression analysis. In RA group, serum APRIL was positively correlated with disease activity score (DAS28-CRP). Serum miR-223 expression was positively correlated with serum miR-155, APRIL levels and with the presence of subcutaneous nodules. Serum miR-155 levels were correlated with antinuclear antibody titer in reverse direction. Conclusion Our results suggest serum APRIL and miR-223 could serve as potential biomarkers of RA, with miR-223 as a predictor of RA risk and APRIL as an excellent biomarker of disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.

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“…Immediately thereafter, B cells can differentiate into autoantibody-producing plasma cells by receiving signals from T cells and stimulation from other factors such as BAFF and APRIL. These autoantibodies form complexes with inflammation- and fibrosis-related antigens, leading to chronic inflammatory damage in the target organ [ 33 , 34 , 35 , 36 , 37 ]. Previous studies have shown that IL-6, a pro-inflammatory cytokine, enhances the inflammatory response and is also an important factor in skin fibrosis [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of TLR7 and TLR9 in the Pathogenesis of Systemic Sclerosis

Wang,

Oishi,

Kobayashi

et al. 2024

IJMS

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The bleomycin-induced scleroderma model is a well-established and dependable method for creating a mouse model of SSc (systemic sclerosis). In the field of skin connective tissue diseases, increasing evidence from clinical and animal experiments suggests that TLRs (Toll-like receptors) play an important role in several diseases. This study aimed to determine the role of TLR7 (Toll-like receptor 7) and TLR9 (Toll-like receptor 9) in the mechanisms of immune abnormalities and fibrosis in SSc. This study used TLR7-KO mice (TLR7-knockout mice with a balb/c background) and TLR9-KO mice (TLR9-knockout mice with a balb/c background) as well as WT mice (wild-type balb/c mice). All three kinds of mice were induced by BLM (bleomycin) in a scleroderma model as the experimental group; meanwhile, WT mice treated with PBS (phosphate-buffered saline) were used as the control group. We analyzed the fibrotic phenotype and the immunological abnormality phenotype of TLR7-deficient and TLR9-deficient mice in the SSc disease model using flow cytometry, RT-PCR (reverse transcription–polymerase chain reaction), a histological examination, and IHC (immunohistochemical staining). In a mouse model of SSc disease, the deletion of TLR7 attenuated skin and lung fibrosis, while the deletion of TLR9 exacerbated skin and lung fibrosis. The deletion of TLR7 resulted in a relative decrease in the infiltration and expression of various pro-inflammatory and fibrotic cells and cytokines in the skin. On the other hand, the deletion of TLR9 resulted in a relative increase in the infiltration and expression of various pro-inflammatory and cytokine-inhibiting cells and cytokines in the skin. Under the influence of pDCs (plasmacytoid dendritic cells), the balances of Beff/Breg (IL-6 + CD19 + B cell/IL-10 + CD19 + B cell), Th17/Treg (IL-17A + CD4 + T cell/Foxp3 + CD25 + CD4 + T cell), M1/M2 (CD86 + macrophage/CD206 + macrophage), and Th1/Th2 (TNFα + CD3 + CD4 + T cell/IL-4 + CD3 + CD4 + T cell) were biased towards the suppression of inflammation and fibrosis as a result of the TLR7 deletion. Comparatively, the balance was biased towards promoting inflammation and fibrosis due to the TLR9 deletion. In the SSc model, TLR7 promoted inflammation and fibrosis progression, while TLR9 played a protective role. These results suggest that TLR7 and TLR9 play opposite roles in triggering SSc to produce immune system abnormalities and skin fibrosis.

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BAFF System in Rheumatoid Arthritis: from Pathobiology to Therapeutic Targets

Cited by 6 publications

References 41 publications

The role of BAFF and APRIL in rheumatoid arthritis

The role of BAFF and APRIL in rheumatoid arthritis

Serum a proliferation-inducing ligand and MicroRNA-223 are associated with rheumatoid arthritis: diagnostic and prognostic implications

The Role of TLR7 and TLR9 in the Pathogenesis of Systemic Sclerosis

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